AA

Pharmacologic Therapy: Prevention of Bone Loss (within 12 Months of Injury)

Download as a PDF

Table 5: Studies of Pharmacologic Therapy for Prevention of Bone Loss in the First Year after SCI

Discussion

Evidence for pharmacological prevention of SCI bone loss includes 8 randomized controlled trials (RCT) (n=152 participants) and 1 non-randomized trial (n=24) (Table 5).  These studies were difficult to interpret as a group due to the variability in selection of the pharmacological treatment, primary outcome measure, relatively short durations of follow-up, small sample sizes, and the lack of stratification based on impairment level.  Preventing bone loss immediately following SCI is challenging given the rapid bone resorption especially in AIS A patients.  The majority of studies found bisphosphonates resulted in a reduction of bone loss compared with a control group.  The two studies which report that first generation bisphosphonates (Clodronate) can maintain bone were short in duration (3 month intervention) and participants had less severe injury (paraplegia, incomplete SCI) (Minaire et al. 1981,1987).  In the studies by Pearson and colleagues (1997) and Nance and colleagues (1999), both groups continued to lose bone, except AIS D participants who had bone density preservation in the lower extremity with bisphosphonates while participants with AIS A had the greatest decline in both studies.  A recent study which used a second-generation version of the bisphosphonate, Pamidronate, and a longer intervention period found no significant differences between groups for bone loss after 1 year (Bauman et al. 2005a).  Gilchrist and colleagues (2007) noted a significant difference in BMD at the hip with once weekly Alendronate. Shapiro and colleagues (2007) tested the effect of once yearly IV Zoledronate with significant improvement in BMD at the hip at 6 months that returned to baseline values at 12 months; the control group on the placebo treatment lost bone over the 12 months.  Bubbear et al. (2011) also showed that once yearly IV Zolendronate resulted in less bone loss at the spine and hip over 12 months.  The investigators also highlighted the added benefits of a once yearly IV administration of bisphosphonate, as this eliminates issues surrounding poor patient adherence and the adverse gastrointestinal effects associated with alternate oral therapies. Although there is evidence that bisphosphonates may reduce bone resorption, current medications do not totally prevent BMD decline.  Nonetheless, there is a window of opportunity soon after injury where SLOP prevention may be effective, and there is sufficient evidence of moderate prevention efficacy that patients should be counseled on the available therapies and allowed to ­­make their own decision regarding treatment.

Conclusions

There is level 1 evidence (from 3 RCTs) (Minaire et al. 1981, 1987; Chappard et al. 1995) that oral Tiludronate and Clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia.

There is level 1 evidence (from 1 RCT) (Pearson et al. 1997) that oral Etidronate prevents a decrease in BMD of the hip and knee region in people with incomplete paraplegia or tetraplegia (AIS D impairment) who return to walking within 3 months of the SCI.

There is level 1 evidence (from 1 RCT) (Gilchrist et al. 2007) that once weekly oral Alendronate maintains hip region BMD.

There is level 1 evidence (from 2 RCTs) (Shapiro et al. 2007; Bubbear et al. 2011) that a one-time IV infusion of Zoledronate may reduce bone loss in the hip region during the 12 months following administration.

There is level 1 evidence (from 1 RCT) (Bauman et al. 2005a) that Pamidronate 60mg IV seven times per year and level 2 evidence (from 1 non-randomized prospective controlled trial) (Nance et al. 1999) that Pamidronate 30 mg IV six times per year is not effective for the prevention of BMD loss at the hip and knee region early after SCI in men and women who have motor complete paraplegia or tetraplegia.

  • Bone health management should begin early following SCI, given the significant declines in hip and knee region bone mass in the first year and the associated lifetime increased fracture risk.

    The efficacy of drug interventions appears to be greater when medications are administered early after SCI onset.

  • Oral tiludronate and clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia.

    Oral etidronate prevents a decrease in BMD of the hip and knee region in people
    with incomplete paraplegia or tetraplegia who return to walking.

    Oral alendronate once weekly maintains BMD at the hip.

    Once yearly IV infusion zoledronate may reduce bone loss at the hip during the 12 months following administration.

  • Pamidronate 30 mg IV or 60 mg IV 4x/year is not effective for the prevention of BMD loss at the hip and knee region early after SCI in people with motor complete paraplegia or tetraplegia.